Infectious Disorders - Drug Targets (Formerly Current Drug Targets - Infectious Disorders) - Volume 8, Issue 4, 2008

In spite the great advances on biomedical sciences, and in particular on the analysis of the immune response regarding cells, mechanisms, signaling pathways and genes involved, together with a plethora of genetically modified animal models, infectious diseases still keep increasing in the world population, both on terms of morbidity and mortality. Naive CD4+ T lymphocytes, upon encountering antigen, differentiate to Read More

In addition to the T helper 1 (Th1) and Th2 lymphocyte subsets, two new subpopulations Th17 and regulatory T (Treg) cells have recently been described. Th17 cells, which produce high levels of interleukin (IL)-17, are dependent on the transcription factor orphan nuclear receptor RORC2/RORγt and have been implicated in exacerbating the immune response to infections. Conversely, Treg cells, either thymus-deriv Read More

Toll like receptors (TLR) play a critical role in the recognition and response of pathogens by the innate immune system. Pathogen engagement of the TLR-MyD88 pathway favours the development of a protective Th1-biased T cell response. Interruption of TLR recognition or signalling has profound effects on innate immunity. Agonists or antagonists of specific TLRs modulate the host response to microbial infections and ha Read More

Posttranscriptional regulation of gene expression plays a pivotal role as a fast control system for T-cells and Bcells operating in the defense reactions against rapidly growing infectious agents. The framework of this machinery involves cis-acting elements in the mRNAs of relevant cytokines and trans-acting factors interacting with these elements. The cis- and trans-acting factors enforce rapid mRNA decay with oth Read More

Genome complexity and diversity can be due to Alternative Splicing (AS), a process by which one gene can generate multiple mRNA isoforms and then several proteins. This is part of a normal process of variation on an individual, and when it is disrupted or modified, may trigger disease. To date, there are many pathologies described due to the effects of altered splicing isoforms, and effort is focused on the description of ne Read More

Recent data from a series of laboratories has pinpointed the relevant role of translation control on the regulation of gene expression. In particular, an analysis of T cell activation has led to demonstrate that during this physiological transition about 20% of the regulated mRNAs are controlled at the translation level. Furthermore, modulating the host mRNA translation is one of the mechanisms used by infectious agents to achieve Read More

For many years, there has been an ongoing search for new compounds that can selectively alter gene expression as a new way to treat human disease by addressing targets that are otherwise “undruggable” with traditional pharmaceutical approaches involving small molecules or proteins. RNA interference (RNAi) strategies have raised a lot of attention and several compounds are currently being tested in clinical trials. Viru Read More